Mechanistic Studies on the Synthesis of Pyrrolidines and Piperidines via Copper-Catalyzed Intramolecular C-H Amination

José María Muñoz-Molina; Daniel Bafaluy; Ignacio Funes-Ardoiz; Adiran de Aguirre; Feliu Maseras; Tomás R Belderrain; Pedro J Pérez; Kilian Muñiz

doi:10.1021/acs.organomet.2c00095

Mechanistic Studies on the Synthesis of Pyrrolidines and Piperidines via Copper-Catalyzed Intramolecular C-H Amination

Organometallics. 2022 May 9;41(9):1099-1105. doi: 10.1021/acs.organomet.2c00095. Epub 2022 Apr 29.

Authors

José María Muñoz-Molina¹, Daniel Bafaluy², Ignacio Funes-Ardoiz², Adiran de Aguirre², Feliu Maseras^{2

3}, Tomás R Belderrain¹, Pedro J Pérez¹, Kilian Muñiz²

Affiliations

¹ Laboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Química, Universidad de Huelva, 21007 Huelva, Spain.
² Institute of Chemical Research of Catalonia, ICIQ, The Barcelona Institute of Science and Technology, Av. Països Catalans, 16, 43007 Tarragona, Spain.
³ Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

Abstract

We have recently developed a method for the synthesis of pyrrolidines and piperidines via intramolecular C-H amination of N-fluoride amides using [Tp ^x CuL] complexes as precatalysts [Tp ^x = tris(pyrazolyl)borate ligand and L = THF or CH₃CN]. Herein, we report mechanistic studies on this transformation, which includes the isolation and structural characterization of a fluorinated copper(II) complex, [(Tp^iPr2OH)CuF] [Tp^iPr = hydrotris(3,5-diisopropylpyrazolyl)borate], pertinent to the mechanistic pathway. The effects of the nature of the Tp ^x ligand in the copper catalyst as well as of the halide in the N-X amides employed as reactants have been investigated both from experimental and computational perspectives.